Experimental studies in our laboratory and others have revealed increasing evidence that solid tumors are angiogenesis dependent. To study how tumor angiogenesis is mediated and how it might be inhibited, four new model systems have been developed: (1)\the intracorneal pocket; (2)\the chick embryo chorioallantoic membrane assay; (3)\sustained release polymer pellets; and (4)\cloned capillary endothelial cells. From these methods, it has been found that capillary growth evolves from a series of at least eight sequential events which the vascular endothelial cell displays after it receives an angiogenic stimulus. It also has been discovered that the rate of capillary growth can be increased by mast cells or by heparin, although neither can initiate angiogenesis. Most recently it has been shown that protamine is an angiogenesis inhibitor capable of controlling the growth of pulmonary metastases by containing them in an avascular or hypovascular configuration. Current work on a new class of angiogenesis inhibitors suggests that in certain experimental tumor systems, the primary and its metastases may be eradicated by anti-angiogenesis.